Implantable Microdevice for Evaluating Drug Responses in Patients with Head and Neck Cancers, the Window of Opportunity Study

PRIMARY OBJECTIVE:

I. To evaluate the safety and feasibility of microdevice placement and removal in head and neck cancer patients.

SECONDARY OBJECTIVES:

I. To conduct pharmacokinetic (PK) measurements of drug concentrations around microdevice reservoirs for twenty drugs across multiple therapeutic classes.

II. To perform pharmacodynamic (PD) measurements of tumor and microenvironment response to drugs, including apoptosis indices, immune infiltration, and markers of deoxyribonucleic acid (DNA) damage, using multiplexed immunohistochemistry.

III. To evaluate the likelihood of independent drug or combination response/failure in this pilot population to determine the appropriateness of nominating therapies for further clinical investigation.

IV. To identify biomarkers of tumor response to drugs in head and neck cancers using an established commercially available clinical biomarker assay (comprised of DNA/ribonucleic acid (RNA) sequencing, fragment analysis, immunohistochemistry [IHC] and chromogenic in situ hybridization [ISH]).

V. To explore candidate genes and gene expression patterns correlating with resistance and response to drugs using single-cell RNA sequencing.

VI. To explore local changes in tumor metabolism effects triggered by tested drugs using matrix-assisted laser desorption/ionization (MALDI).

VII. To correlate responses and biomarkers with genomic profiling and clinical tumor phenotypes to build a genotype-phenotype dataset.

OUTLINE:

Patients undergo placement of 1-5 microdevices to receive standard of care drugs (lenvatinib, axitinib, tretinoin, venetoclax, pembrolizumab, nivolumab, cisplatin, carboplatin, vinorelbine, paclitaxel, docetaxel, fluorouracil, cetuximab) 3-5 days later patients then undergo standard of care surgery or retrieval of microdevices. Patients also undergo magnetic resonance imaging (MRI), computed tomography (CT) scan, and collection of blood samples throughout the trial.

After completion of study treatment, patients are followed every 4 months for up to 2 years.